A novel form of vitamin B3 found in milk in small quantities produces remarkable health benefits in mice when high doses are administered, according to a new study conducted by researchers at Weill Cornell Medical College and the Polytechnic School in Lausanne, Switzerland.
The findings, recently reported in the June 2012 issue of the journal, Cell Metabolism, reveal that high doses of the vitamin precursor, nicotinamide riboside (NR) — a cousin of niacin — prevent obesity in mice that are fed a fatty diet, and also increase muscle performance, improve energy expenditure and prevent diabetes development, all without side effects.
The Swiss researchers, led by Dr. Johan Auwerx, performed the mouse experiments, while the ability to give the animals sufficient doses of NR was made possible by Weill Cornell Medical College researchers, who played key roles in uncovering the biological story of NR.
"This study is very important. It shows that in animals, the use of NR offers the health benefits of a low-calorie diet and exercise — without doing either one," says Dr. Anthony Sauve, associate professor of Pharmacology at Weill Cornell Medical College.
Dr. Sauve is the pharmacologist and organic chemist who has invented a simple method for efficiently synthesizing NR in large scale. He was first to show that NR increases nicotinamide adenine dinucleotide (NAD) levels in mammalian cells. NAD is a central player in energy metabolism. He has pioneered research into the compound, and he is a leader in investigating how NAD can signal adaptation in cells and in physiology.
"The research also suggests that the effects of NR could be even broader," Dr. Sauve says. "The bottom line is that NR improves the function of mitochondria, the cell's energy factories. Mitochondrial decline is the hallmark of many diseases associated with aging, such as cancer and neurodegeneration, and NR supplementation boosts mitochondrial functioning."
The Swiss researchers call NR a "hidden vitamin" that is believed to also be present in many other foods, although levels are low and difficult to measure. Nevertheless, the effects of NR on metabolism "are nothing short of astonishing."
Got nicotinamide riboside?
The study depended on a series of crucial discoveries by Dr. Sauve and his laboratory colleagues.
NR, related to niacin and other common forms of vitamin B3, was first investigated more than 60 years ago by a Stanford researcher and 1959 Nobel Laureate, Arthur Kornberg. But little more was known about its effects in mammals until Dr. Sauve discovered the effect NR had in stimulating levels of NAD in mammalian cells — work he published in 2007.
NAD allows sugars, fats, and proteins to be converted into energy. Dr. Sauve's research provided the first evidence that NR enhances NAD levels in the mitochondria in mammalian cells in culture. These findings are published in the current study. These cell-based observations were key to the demonstration that NR could stimulate tissue NAD levels in animals, and that it could stimulate NAD-dependent sirtuins, which adapt physiology to the low calorie diets that are known to extend the lifespan of many organisms.
Dr. Sauve invented a relatively simple method for efficiently synthesizing NR in large scale so that its health benefits can be studied. This methodology, which makes it possible to make NR commercially available, was patented by Cornell's Center for Technology Enterprise and Commercialization and subsequently licensed to ChromaDex Corporation.
The development of a means to synthesize NR in adequate quantities was crucial to the current research, and the Sauve lab provided methods and NR to make the study possible. In addition, the biological observations on the effects of NR on NAD levels in cells and on mitochondria were key to the study. Finally, the Sauve laboratory has developed state of the art analytical methods to determine NAD levels in cells, tissues and organelles, and the laboratory provided several key metabolic measurements highlighted in the study.
"Our published scientific work has verified that NR is perhaps the most potent NAD enhancing agent ever identified," he says. His laboratory is also widely recognized for developing an expertise in the measurement of NAD metabolism in cell tissues.
With this compound, the Swiss researchers found that mice on a high-fat diet supplemented with NR gained significantly less weight (60 percent) than mice fed the same diet without NR, even though the mice supplemented with NR ate the same amount of food as mice on the high fat diet not treated with NR. They had improved energy. They were in better shape than the untreated mice, with significantly better endurance and stronger muscles. Additionally, none of the treated mice developed diabetes, as seen in the untreated mice on the high fat diet. And when fed a normal diet, NR treated mice had improved sensitivity to insulin. The NR treated mice also showed lower cholesterol levels. All of these benefits came without toxicity.While the new study demonstrates that high doses of NR can largely prevent the negative health consequences of a poor diet in mice, Dr. Sauve stresses that the effects of high doses of the vitamin in humans have not been evaluated. "It is important to keep in mind that the amount of NR in milk and other foods appears to be small. We don't know what effects NR would have in humans at relatively high doses," he says.
The study's senior investigator Dr. Auwerx is head of Laboratory of Integrative Systems Physiology at the Polytechnic School in Lausanne (École Polytechnique Fédérale de Lausanne or EPFL) and the first author is Dr. Carles Cantó, also of EPFL.
Other co-authors include Dou Y. Youn and Dr. Yana Cen from Weill Cornell Medical College; Dr. Riekelt H. Houtkooper, Dr. Eija Pirinen, Dr. Maaike H. Oosterveer, Dr. Pablo J. Fernandez-Marcos, Dr. Hiroyasu Yamamoto, Dr. Pénélope A. Andreux, Dr. Philippe Cettour-Rose, Dr. Kristina Schoonjans and Dr. Chris Rinsch from EPFL; Dr. Karl Gademann from the University of Basel in Switzerland.
The Ellison Medical Foundation New Scholar Award and the New York State Spinal Cord Injury Board funded study contributions by the Weill Cornell Medical College researchers.
Weill Cornell Medical College
Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances — including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston.
Exciting Plant Vacuoles
14.06.2019 | Julius-Maximilians-Universität Würzburg
A microscopic topographic map of cellular function
13.06.2019 | University of Missouri-Columbia
Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.
Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...
Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.
The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...
Discovery by Brazilian and US researchers could change the classification of two species, which appear more akin to jellyfish than was thought.
The tube anemone Isarachnanthus nocturnus is only 15 cm long but has the largest mitochondrial genome of any animal sequenced to date, with 80,923 base pairs....
Researchers at Chalmers University of Technology, Sweden, have discovered a completely new way of capturing, amplifying and linking light to matter at the nanolevel. Using a tiny box, built from stacked atomically thin material, they have succeeded in creating a type of feedback loop in which light and matter become one. The discovery, which was recently published in Nature Nanotechnology, opens up new possibilities in the world of nanophotonics.
Photonics is concerned with various means of using light. Fibre-optic communication is an example of photonics, as is the technology behind photodetectors and...
Fraunhofer IZM is joining the EUROPRACTICE IC Service platform. Together, the partners are making fan-out wafer level packaging (FOWLP) for electronic devices available and affordable even in small batches – and thus of interest to research institutes, universities, and SMEs. Costs can be significantly reduced by up to ten customers implementing individual fan-out wafer level packaging for their ICs or other components on a multi-project wafer. The target group includes any organization that does not produce in large quantities, but requires prototypes.
Research always means trying things out and daring to do new things. Research institutes, universities, and SMEs do not produce in large batches, but rather...
29.04.2019 | Event News
17.04.2019 | Event News
15.04.2019 | Event News
14.06.2019 | Information Technology
14.06.2019 | Materials Sciences
14.06.2019 | Medical Engineering